The purpose of this project is to understand the molecular mechanism by chich genes for connective tissue proteins are differentially regulated and expressed during normal development and in disease states. We are using recombinant DNA technology and conventional methods in nucleic acid biochemistry to study the structure and expression of genes coding for extracellular and cell associasted structural proteins that are affected during development and in pathologic states. To study normal and abnormal cartilage development, we are examining the molecular basis for loss of phenotypic traits of chondrocytes after exposure to the thymidine analog 5-bromodeoxyuridine. Recombinant cDNA and genomic clones of collagen types I and II are being used to analyze the RNA and DNA of differentiated and dedifferentiated cartilage cells. We have also synthesized specific recombinant clones to study the coordinated regulation of the synthesis of the two component chains of type I collagen. In addition, a cDNA library is currently under construction to identify and study the genes for the basement membrane constituents, type IV collagen and its attachment protein, laminin.